Programmed cell death is important for the development of the nervous system in general, and the visual system in particular. In the developing Drosophila compound eye, programmed cell death plays a major role at two stages: in the third instar disc, close to the morphogenetic furrow, and later, in the mid-pupa, at the end of the process of ommatidial cell recruitment, when it eliminates excess cells. A number of alleles of the roughest gene are known, and they can affect programmed cell death as well as other aspects of development. The gene roughest encodes a trans-membrane protein which can mediate homophilic adhesion when expressed on tissue culture cells, and may act as a receptor for a programmed cell death-inducing signal. Two alleles (rstCT and rst3) are weak mutations which affect the C-terminal domain of Roughest and have more specific effects on programmed cell death in the eye. The rst3 allele has been made the basis of an interaction screen to find other genes involved in retinal programmed cell death. The focus of this proposal is the study of these genes, and their developmental and molecular functions.